Gamma-glutamyl metformin inhibits renal cell carcinoma progression by activating AMPK signaling pathway

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Updated: May 26, 2026

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

Zheng Lv1,2, Li Song Zhang3, Awuti Aisha4

  • 1Department of Urology, Central Hospital, Tianjin University/Tianjin Third Central Hospital, Tianjin, China.

Frontiers in Pharmacology
|May 25, 2026
PubMed

Insights

A novel gamma-glutamyl metformin (γE-Met) prodrug targets renal cell carcinoma (RCC) by leveraging Gamma-glutamyl transpeptidase (GGT) overexpression. This GGT-responsive drug enhances metformin

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Metformin shows potential for renal cell carcinoma (RCC) treatment, but its anti-tumor mechanisms require further elucidation.
  • Gamma-glutamyl transpeptidase (GGT) is overexpressed in RCC tissues, serving as a potential biomarker.
  • Targeted drug delivery systems are needed to enhance metformin's efficacy in RCC therapy.

Purpose of the Study:

  • To develop and evaluate a novel metformin prodrug, gamma-Glutamyl Metformin (γE-Met), for targeted RCC therapy.
  • To investigate the GGT-specific release of metformin from γE-Met in RCC cells.
  • To assess the anti-tumor activity of γE-Met by activating the AMP-activated protein kinase (AMPK) signaling pathway.

Main Methods:

  • Synthesis and characterization of gamma-Glutamyl Metformin (γE-Met).
  • In vitro studies assessing GGT-catalyzed metformin release in RCC cells.
  • Evaluation of γE-Met's effect on cell growth, metastasis, and AMPK pathway activation.
  • Comparison of therapeutic efficacy between γE-Met and metformin.

Main Results:

  • γE-Met specifically releases metformin in GGT-overexpressing RCC cells.
  • The prodrug prolongs metformin retention time within tumor cells.
  • γE-Met significantly inhibits renal cancer cell growth and metastasis.
  • Activation of the AMPK signaling pathway was observed.

Conclusions:

  • GGT-responsive γE-Met demonstrates enhanced therapeutic efficacy compared to metformin for RCC.
  • γE-Met represents a promising metformin prodrug for targeted RCC treatment.
  • The development of γE-Met holds substantial clinical application prospects.
Keywords:
AMPK signaling pathwaygamma-glutamyl transpeptidasemetforminprodrugrenal cancer

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